Journal
CLINICAL CANCER RESEARCH
Volume 16, Issue 7, Pages 2131-2137Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1078-0432.CCR-09-3323
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Funding
- Ministry of Education, Science and Technology [2009-0063255, 2009-0068819]
- National Research Foundation of Korea [2009-0068819] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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Purpose: Intravesical Bacillus Calmette-Guerin (BCG) immunotherapy is effective in the prevention of recurrence and progression in many cases of nonmuscle invasive bladder cancer, but many patients fail to respond. The aim of this study was to identify gene sets of markers that could predict the response to BCG immunotherapy in primary pT1 bladder cancer using microarray gene expression profiling. Experimental Design: We used 80 patients with primary pT1 bladder cancer treated with BCG immunotherapy as training (48) and test (32) sets. Microarray gene expression profiling was done in the training set to identify genes differentially expressed between responder and nonresponder to BCG immunotherapy according to the events (recurrence or progression). Using a real-time reverse-transcriptase PCR, our findings were validated in the test set. Results: In the training set, 424 and 287 genes were significantly associated with recurrence-and progression-free survival, respectively. Functional annotation of these genes included cell-mediated immune response, inflammatory response, cellular growth, and proliferation. From these predictive gene signatures, 24 genes (12 in recurrence and 12 in progression) with the highest score of expression ratio were extracted for validation in the test set. In multivariate regression analyses, predictive gene signatures were the only independent predictors of recurrence (hazard ratio, 3.38; P = 0.048) or progression (hazard ratio, 10.49; P = 0.048) in the test set. Conclusions: Predictive gene signatures have diagnostic value for determining the response to intravesical BCG immunotherapy in primary pT1 bladder cancer. Clin Cancer Res; 16(7); 2131-7. (C)2010 AACR.
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